- Email: [email protected]
Ventricular Tachycardia and Tuberculous Lymphadenopathy
JACC VOL. 65, NO. 2, 2015
Letters
218
JANUARY 20, 2015:217–23
Despite these limitations, we demonstrate the
F I G U R E 1 Trends of Mortality in Patients With AMI From 2000 to 2008 and the
disappearance of the weekend effect for AMI. This
Cumulative Percentage of Cardiac Catheterization Since Day of Admission
has important implications for other time-sensitive
2000-2002
2003-2005
2007
2008
2005
2007
20
2006-2008
Cumulative Percentage of Cardiac Catheterization
100 90 80 70 60 50 40 30 20 10 0
Gagan Kumar, MD Abhishek Deshmukh, MD Ankit Sakhuja, MD Amit Taneja, MD Nilay Kumar, MD Elizabeth Jacobs, MD *Rahul Nanchal, MD From the Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) Group of Investigators
30
2008
2005
2006
2003
2004
2001
B
2002
2000
5
regardless of the day of admission.
40
2006
7 6
that have led to persons receiving equivalent care,
50
2003
8
systems should strive to emulate processes for AMI 60
2004
9
where the weekend effect persists (5). Health care
70
2001
10
2000
In-hospital Mortality (%)
11
2002
% of Patients Undergoing Cardiac Catheterization on Day of Admission
A
disease processes, such as pulmonary embolism,
Weekend
Weekday
*Division of Pulmonary and Critical Care 0
1 2 3 4 5 Days from Admission
6
0
1 2 3 4 5 Days from Admission
6
0
1 2 3 4 5 Days from Admission
6
Medical College of Wisconsin 9200 West Wisconsin Avenue
(A) The error bars represent standard error of mean. (B) Looking at weekday versus
Milwaukee, Wisconsin 53226
weekend admissions, this chart compares the 3 epochs (2000 to 2002, 2003 to 2005, and
E-mail: [email protected]
2006 to 2008). AMI ¼ acute myocardial infarction.
http://dx.doi.org/10.1016/j.jacc.2014.09.083
REFERENCES
time periods 2000 to 2002 (adjusted OR: 0.70; 95% CI: 0.68 to 0.72; p < 0.001) and 2003 to 2005 (adjusted OR: 0.79; 95% CI: 0.77 to 0.81; p < 0.001) when compared with weekends during 2006 to 2008 (adjusted OR: 0.88; 95% CI: 0.85 to 0.91; p < 0.001) (interaction p value for both time periods <0.01). Changes over time in rates of cardiac catheterization likely reflect the more liberal use of primary PCI and better adherence to guideline recommendations due to public reporting and government oversight of compliance with core measures. Limitations of our study include varying coding practices across U.S. hospitals, although these are
1. Kostis WJ, Demissie K, Marcella SW, et al. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med 2007;356: 1099–109. 2. Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project. Introduction to the HCUP Nationwide Inpatient Sample (NIS) 2008. Available at: http://www.hcup-us.ahrq.gov/db/nation/nis/NIS_Introduction_2 008.jsp. Accessed June 17, 2014. 3. Petersen LA, Wright S, Normand SL, Daley J. Positive predictive value of the diagnosis of acute myocardial infarction in an administrative database. J Gen Intern Med 1999;14:555–8. 4. Magid DJ, Wang Y, Herrin J, et al. Relationship between time of day, day of week, timeliness of reperfusion, and in-hospital mortality for patients with acute ST-segment elevation myocardial infarction. JAMA 2005;294: 803–12. 5. Nanchal R, Kumar G, Taneja A, et al. Pulmonary embolism: the weekend effect. Chest 2012;142:690–6.
unlikely to differ between weekdays and weekends in a given hospital. We do not have data for time of onset of chest pain, medications used, electrocardiographic findings, cardiac biomarkers, and coronary angiography findings due to the administrative nature of the NIS database. If available, these details would have allowed us to adjust for confounders more robustly. Inability to determine the cause
Ventricular Tachycardia and Tuberculous Lymphadenopathy Sign of Myocardial Tuberculosis?
of death also limits our interpretation of results. Therefore, despite multivariable adjustment, we cannot exclude unmeasured confounders as a cause
Myocardial tuberculosis (TB) is an exceptionally rare
for our results. Finally, the time to procedure is coded
form of extrapulmonary TB (1). It is a serious illness
in days and not in hours or minutes. This has signif-
with
icance, as door-to-balloon times are typically quoted
blocks, ventricular failure, malignant ventricular ar-
in minutes.
rhythmias, and sudden cardiac death) and has been
varied
clinical
manifestations
(conduction
JACC VOL. 65, NO. 2, 2015
Letters
JANUARY 20, 2015:217–23
T A B L E 1 Baseline Characteristics and Response to Treatment
Patient #
1
2
3
4
5
6
7
8
9
10
11
12
13
Age, yrs
52
24
44
35
39
51
40
52
50
46
52
34
13
Sex
M
F
M
F
M
M
F
F
M
F
M
M
F
Duration since symptom onset, days
180
49
270
360
90
17
25
10
51
16
150
22
2
Clinical presentation
VT*
CCF
VT
CCF
VT
VT*
VT
VT
VT*
VT*
VT
VT
VT
LN involvement (peripheral/mediastinal)
+/+
–/+
+/–
+/–
+/–
+/–
+/+
–/+
+/+
+/+
+/+
–/+
+/+
+
+
–
ND
–
+
+
+
ND
+
+
ND
+ +
Myocardial scar by MRI at baseline Diagnosis of TB Mtb PCR
–
–
+
+
+
–
+
–
–
+
–
+
Smear
–
+
–
+
–
–
–
–
–
–
–
–
–
Mtb culture
+
+
+
–
+
+
+
+
+
+
+
+
+
B
1
NA
13
NA
4
>35
10
5
†
4
4
31
2
A
0
0
0
0
0
0
0
0
†
0
0
0
0
VT episodes
LV ejection fraction, % B
40
27
55
20
62
40
56
47
35
40
58
65
63
A
46
22
60
22
64
58
56
47
36
48
63
71
68
Myocardium
ND
[
–
ND
/
/
–
[
Y
–
–
/
Y
Lymph node
ND
–
–
ND
–
–
–
Y
–
–
–
Y
–
18F-FDG uptake in PET-CT compared to baseline
*Left ventricular ejection fraction $40%; þ present/positive; absent/negative. A ¼ after initial phase of anti-TB treatment; B ¼ before initiation of anti-TB treatment; CCF ¼ congestive cardiac failure; F ¼ female; FDG ¼ fluorodeoxyglucose; LN ¼ lymph node; LVEF ¼ left ventricular ejection fraction; M ¼ male; MRI ¼ magnetic resonance imaging; ND ¼ not determined; PCR ¼ polymerase chain reaction; PET/CT ¼ positron emission computed tomography; TB ¼ tuberculosis; VT ¼ ventricular tachycardia.
occasionally documented in case reports (2,3). In this
Tuberculin skin test (5 tuberculin units) result
report, we describe our experience in the clinical
was positive in 11 patients. Baseline erythrocyte
recognition and management of myocardial TB, asso-
sedimentation rate (first hour) was elevated in 10 pa-
ciated with mediastinal and/or peripheral lymphade-
tients. All patients were seronegative for human im-
nopathy in 13 patients presenting with unexplained
munodeficiency virus. Serum angiotensin-converting
ventricular tachycardia (VT) or heart failure. None of
enzyme levels were within normal limits in all pa-
these patients manifested constitutional symptoms or
tients. Biopsy specimens were sampled from those
clinical features that were suggestive of TB. We
lymph nodes showing the highest metabolic activity
believe that this entity is an under-recognized cause of
on PET/CT scan. Histopathology revealed epithelioid
ventricular arrhythmia and ventricular dysfunction
granulomas in all patients and caseating necrosis
that can be treated successfully.
in 8 patients. The diagnosis of TB was made by
The predominant symptom seen in 10 of the 13 pa-
lymph node biopsy based on a positive Ziehl–Neelsen
tients was palpitations with or without pre-syncope.
stain for acid-fast bacilli, Lowenstein–Jensen culture
Eleven patients presented with sustained VT, and
for Mycobacterium tuberculosis, and/or a positive TB
2 patients presented with congestive heart failure.
polymerase chain reaction. Right ventricular endo-
Electrocardiogram revealed right bundle branch block
myocardial biopsy was negative in all 5 patients in
in 2 patients and nonspecific T-wave changes in 1 pa-
whom it was performed.
tient. The chest radiograph was normal in all patients.
All patients received daily self-supervised standard
Echocardiogram revealed left ventricular dysfunction
anti-TB treatment comprising rifampicin, isoniazid,
in 6 patients with no other significant abnormality
pyrazinamide, and ethambutol for the first 2 months
evident. Coronary artery disease was ruled out in all
(intensive phase), followed by rifampicin and isoni-
adult patients. Mid-myocardial scar was present in 8 of
azid for the subsequent 7 to 10 months (continuation
the 10 patients in whom delayed enhancement cardiac
phase). The patients also received oral prednisolone
magnetic resonance imaging was performed. Positron
(1 mg/kg/day) that was tapered over 3 months. All
emission tomography/computed tomography (PET/
patients also received antiarrhythmic drugs and/or
CT) of the chest with 18-fluorodeoxyglucose revealed
drugs for heart failure. An implantable cardioverter
increased fluorodeoxyglucose uptake in the myocar-
defibrillator was recommended in all patients who
dium and lymph nodes in all patients.
presented with VT. Radiofrequency catheter ablation
219
220
JACC VOL. 65, NO. 2, 2015
Letters
JANUARY 20, 2015:217–23
was completed in 4 patients with incessant VT: before
REFERENCES
the diagnosis of TB in 1 patient and during anti-TB
1. Sharma SK, Mohan A. Tuberculosis: from an incurable scourge to a curable
treatment in the remaining 3 patients. Patients were
disease—journey over a millennium. Indian J Med Res 2013;137:455–93.
followed up at 1, 3, and 6 months after the initiation of
2. Kanchan T, Nagesh KR, Lobo FD, et al. Tubercular granuloma in the myocardium. Singapore Med J 2010;51:e15–7.
anti-TB treatment and when clinically warranted. The response was assessed after the intensive phase of anti-TB treatment in terms of clinical improvement, change in ejection fraction by echocardiography, and change in 18-fluorodexoyglucose uptake by PET/CT. There was significant improvement in ejection
3. Gulati GS, Kothari SS. Diffuse infiltrative cardiac tuberculosis. Ann Pediatr Cardiol 2011;4:87–9. 4. Thachil A, Christopher J, Sastry BK, et al. Monomorphic ventricular tachycardia and mediastinal adenopathy due to granulomatous infiltration in patients with preserved ventricular function. J Am Coll Cardiol 2011;58: 48–55.
fraction (mean 46.7 14.4% to 50.8 16.1%; p ¼ 0.009). All patients but 1 became free of VT. In a follow-up PET/CT (n ¼ 11), abnormal metabolic activity resolved completely in the myocardium in 4 patients and in the lymph nodes in 9 patients (Table 1). There were no deaths.
Increased Mortality by Digoxin in Patients With Atrial Fibrillation?
Our observations suggest that TB can present as idiopathic VT or unexplained ventricular dysfunction;
In the TREAT-AF (Retrospective Evaluation and
patients may not have constitutional symptoms.
Assessment of Therapies in AF) study (1), the effect of
Biopsy
targeting
fluorodeoxyglucose-avid
lymph
digoxin on overall mortality in patients with incident
nodes rather than endomyocardial biopsy is more
atrial fibrillation (AF) was studied. In this observa-
useful in making a clinical diagnosis. It may be prudent
tional study, after adjustment for potential con-
to investigate all patients with unexplained VT or left
founders with the Cox proportional hazards model
ventricular dysfunction and lymphadenopathy for
and propensity score analyses, digoxin was associ-
myocardial TB, especially in those areas where the
ated with an increased risk (21% to 24%) of death. The
prevalence of TB is high. By subjecting the biopsy
investigators extensively discussed the potential
specimen to mycobacterial culture, TB polymerase
limitations of their study, but I have 2 questions
chain reaction and histopathologic examination will
about the design choices.
help in distinguishing between TB and sarcoidosis—
First, the investigators stated that patients were
another granulomatous condition that may present in
placed in the digoxin group versus the reference
a similar fashion (4). This report serves to highlight the
group on the basis of use of digoxin within the first
fact that myocardial TB may be more common than
90 days after the diagnosis of AF. Digoxin is the first
believed. Early diagnosis is important to prevent
choice for therapy in patients with AF complicated by
morbidity and mortality.
heart failure and the second choice in patients whose
Alladi Mohan, MD Ajit Thachil, MD, DM Gomathi Sundar, PG, PA B.K.S. Sastry, MD, DM Ashfaq Hasan, MD C. Sridevi, MD, DNB *Calambur Narasimhan, MD, DM *CARE Hospital Department of Cardiac Electrophysiology Road No. 1, Banjara Hills Hyderabad, Telangana India 500 034 E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2014.09.087 Please note: Dr. Narasimhan has received research grants from Biosense Webster, Inc., Medtronic, Inc., and St. Jude Medical, Inc.; and a fellowship grant from Medtronic, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors thank John G. Cleland, Foundation Chair of Cardiology at the University of Hull, for useful suggestions.
first choices for treatment of AF, beta-blockers and calcium
channel
antagonists,
are
not
effective
enough. When only the first 90 days are used for exposure classification, there may be a substantial misclassification of digoxin in both the digoxin group and the reference group. The fact that the medication possession ratio of digoxin was only calculated for the digoxin group does not take into account such misclassification. Second,
the
investigators
stated
that
they
adjusted for the medication possession ratio in the multivariate Cox analysis. I do not understand this: how can you adjust for a variable that is zero in all patients in the reference group and a certain number between zero and one in the digoxin group? I believe the appropriate analysis would be to stratify the digoxin group with different medication possession ratios and compare these with the reference group.
Letters
218
JANUARY 20, 2015:217–23
Despite these limitations, we demonstrate the
F I G U R E 1 Trends of Mortality in Patients With AMI From 2000 to 2008 and the
disappearance of the weekend effect for AMI. This
Cumulative Percentage of Cardiac Catheterization Since Day of Admission
has important implications for other time-sensitive
2000-2002
2003-2005
2007
2008
2005
2007
20
2006-2008
Cumulative Percentage of Cardiac Catheterization
100 90 80 70 60 50 40 30 20 10 0
Gagan Kumar, MD Abhishek Deshmukh, MD Ankit Sakhuja, MD Amit Taneja, MD Nilay Kumar, MD Elizabeth Jacobs, MD *Rahul Nanchal, MD From the Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) Group of Investigators
30
2008
2005
2006
2003
2004
2001
B
2002
2000
5
regardless of the day of admission.
40
2006
7 6
that have led to persons receiving equivalent care,
50
2003
8
systems should strive to emulate processes for AMI 60
2004
9
where the weekend effect persists (5). Health care
70
2001
10
2000
In-hospital Mortality (%)
11
2002
% of Patients Undergoing Cardiac Catheterization on Day of Admission
A
disease processes, such as pulmonary embolism,
Weekend
Weekday
*Division of Pulmonary and Critical Care 0
1 2 3 4 5 Days from Admission
6
0
1 2 3 4 5 Days from Admission
6
0
1 2 3 4 5 Days from Admission
6
Medical College of Wisconsin 9200 West Wisconsin Avenue
(A) The error bars represent standard error of mean. (B) Looking at weekday versus
Milwaukee, Wisconsin 53226
weekend admissions, this chart compares the 3 epochs (2000 to 2002, 2003 to 2005, and
E-mail: [email protected]
2006 to 2008). AMI ¼ acute myocardial infarction.
http://dx.doi.org/10.1016/j.jacc.2014.09.083
REFERENCES
time periods 2000 to 2002 (adjusted OR: 0.70; 95% CI: 0.68 to 0.72; p < 0.001) and 2003 to 2005 (adjusted OR: 0.79; 95% CI: 0.77 to 0.81; p < 0.001) when compared with weekends during 2006 to 2008 (adjusted OR: 0.88; 95% CI: 0.85 to 0.91; p < 0.001) (interaction p value for both time periods <0.01). Changes over time in rates of cardiac catheterization likely reflect the more liberal use of primary PCI and better adherence to guideline recommendations due to public reporting and government oversight of compliance with core measures. Limitations of our study include varying coding practices across U.S. hospitals, although these are
1. Kostis WJ, Demissie K, Marcella SW, et al. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med 2007;356: 1099–109. 2. Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project. Introduction to the HCUP Nationwide Inpatient Sample (NIS) 2008. Available at: http://www.hcup-us.ahrq.gov/db/nation/nis/NIS_Introduction_2 008.jsp. Accessed June 17, 2014. 3. Petersen LA, Wright S, Normand SL, Daley J. Positive predictive value of the diagnosis of acute myocardial infarction in an administrative database. J Gen Intern Med 1999;14:555–8. 4. Magid DJ, Wang Y, Herrin J, et al. Relationship between time of day, day of week, timeliness of reperfusion, and in-hospital mortality for patients with acute ST-segment elevation myocardial infarction. JAMA 2005;294: 803–12. 5. Nanchal R, Kumar G, Taneja A, et al. Pulmonary embolism: the weekend effect. Chest 2012;142:690–6.
unlikely to differ between weekdays and weekends in a given hospital. We do not have data for time of onset of chest pain, medications used, electrocardiographic findings, cardiac biomarkers, and coronary angiography findings due to the administrative nature of the NIS database. If available, these details would have allowed us to adjust for confounders more robustly. Inability to determine the cause
Ventricular Tachycardia and Tuberculous Lymphadenopathy Sign of Myocardial Tuberculosis?
of death also limits our interpretation of results. Therefore, despite multivariable adjustment, we cannot exclude unmeasured confounders as a cause
Myocardial tuberculosis (TB) is an exceptionally rare
for our results. Finally, the time to procedure is coded
form of extrapulmonary TB (1). It is a serious illness
in days and not in hours or minutes. This has signif-
with
icance, as door-to-balloon times are typically quoted
blocks, ventricular failure, malignant ventricular ar-
in minutes.
rhythmias, and sudden cardiac death) and has been
varied
clinical
manifestations
(conduction
JACC VOL. 65, NO. 2, 2015
Letters
JANUARY 20, 2015:217–23
T A B L E 1 Baseline Characteristics and Response to Treatment
Patient #
1
2
3
4
5
6
7
8
9
10
11
12
13
Age, yrs
52
24
44
35
39
51
40
52
50
46
52
34
13
Sex
M
F
M
F
M
M
F
F
M
F
M
M
F
Duration since symptom onset, days
180
49
270
360
90
17
25
10
51
16
150
22
2
Clinical presentation
VT*
CCF
VT
CCF
VT
VT*
VT
VT
VT*
VT*
VT
VT
VT
LN involvement (peripheral/mediastinal)
+/+
–/+
+/–
+/–
+/–
+/–
+/+
–/+
+/+
+/+
+/+
–/+
+/+
+
+
–
ND
–
+
+
+
ND
+
+
ND
+ +
Myocardial scar by MRI at baseline Diagnosis of TB Mtb PCR
–
–
+
+
+
–
+
–
–
+
–
+
Smear
–
+
–
+
–
–
–
–
–
–
–
–
–
Mtb culture
+
+
+
–
+
+
+
+
+
+
+
+
+
B
1
NA
13
NA
4
>35
10
5
†
4
4
31
2
A
0
0
0
0
0
0
0
0
†
0
0
0
0
VT episodes
LV ejection fraction, % B
40
27
55
20
62
40
56
47
35
40
58
65
63
A
46
22
60
22
64
58
56
47
36
48
63
71
68
Myocardium
ND
[
–
ND
/
/
–
[
Y
–
–
/
Y
Lymph node
ND
–
–
ND
–
–
–
Y
–
–
–
Y
–
18F-FDG uptake in PET-CT compared to baseline
*Left ventricular ejection fraction $40%; þ present/positive; absent/negative. A ¼ after initial phase of anti-TB treatment; B ¼ before initiation of anti-TB treatment; CCF ¼ congestive cardiac failure; F ¼ female; FDG ¼ fluorodeoxyglucose; LN ¼ lymph node; LVEF ¼ left ventricular ejection fraction; M ¼ male; MRI ¼ magnetic resonance imaging; ND ¼ not determined; PCR ¼ polymerase chain reaction; PET/CT ¼ positron emission computed tomography; TB ¼ tuberculosis; VT ¼ ventricular tachycardia.
occasionally documented in case reports (2,3). In this
Tuberculin skin test (5 tuberculin units) result
report, we describe our experience in the clinical
was positive in 11 patients. Baseline erythrocyte
recognition and management of myocardial TB, asso-
sedimentation rate (first hour) was elevated in 10 pa-
ciated with mediastinal and/or peripheral lymphade-
tients. All patients were seronegative for human im-
nopathy in 13 patients presenting with unexplained
munodeficiency virus. Serum angiotensin-converting
ventricular tachycardia (VT) or heart failure. None of
enzyme levels were within normal limits in all pa-
these patients manifested constitutional symptoms or
tients. Biopsy specimens were sampled from those
clinical features that were suggestive of TB. We
lymph nodes showing the highest metabolic activity
believe that this entity is an under-recognized cause of
on PET/CT scan. Histopathology revealed epithelioid
ventricular arrhythmia and ventricular dysfunction
granulomas in all patients and caseating necrosis
that can be treated successfully.
in 8 patients. The diagnosis of TB was made by
The predominant symptom seen in 10 of the 13 pa-
lymph node biopsy based on a positive Ziehl–Neelsen
tients was palpitations with or without pre-syncope.
stain for acid-fast bacilli, Lowenstein–Jensen culture
Eleven patients presented with sustained VT, and
for Mycobacterium tuberculosis, and/or a positive TB
2 patients presented with congestive heart failure.
polymerase chain reaction. Right ventricular endo-
Electrocardiogram revealed right bundle branch block
myocardial biopsy was negative in all 5 patients in
in 2 patients and nonspecific T-wave changes in 1 pa-
whom it was performed.
tient. The chest radiograph was normal in all patients.
All patients received daily self-supervised standard
Echocardiogram revealed left ventricular dysfunction
anti-TB treatment comprising rifampicin, isoniazid,
in 6 patients with no other significant abnormality
pyrazinamide, and ethambutol for the first 2 months
evident. Coronary artery disease was ruled out in all
(intensive phase), followed by rifampicin and isoni-
adult patients. Mid-myocardial scar was present in 8 of
azid for the subsequent 7 to 10 months (continuation
the 10 patients in whom delayed enhancement cardiac
phase). The patients also received oral prednisolone
magnetic resonance imaging was performed. Positron
(1 mg/kg/day) that was tapered over 3 months. All
emission tomography/computed tomography (PET/
patients also received antiarrhythmic drugs and/or
CT) of the chest with 18-fluorodeoxyglucose revealed
drugs for heart failure. An implantable cardioverter
increased fluorodeoxyglucose uptake in the myocar-
defibrillator was recommended in all patients who
dium and lymph nodes in all patients.
presented with VT. Radiofrequency catheter ablation
219
220
JACC VOL. 65, NO. 2, 2015
Letters
JANUARY 20, 2015:217–23
was completed in 4 patients with incessant VT: before
REFERENCES
the diagnosis of TB in 1 patient and during anti-TB
1. Sharma SK, Mohan A. Tuberculosis: from an incurable scourge to a curable
treatment in the remaining 3 patients. Patients were
disease—journey over a millennium. Indian J Med Res 2013;137:455–93.
followed up at 1, 3, and 6 months after the initiation of
2. Kanchan T, Nagesh KR, Lobo FD, et al. Tubercular granuloma in the myocardium. Singapore Med J 2010;51:e15–7.
anti-TB treatment and when clinically warranted. The response was assessed after the intensive phase of anti-TB treatment in terms of clinical improvement, change in ejection fraction by echocardiography, and change in 18-fluorodexoyglucose uptake by PET/CT. There was significant improvement in ejection
3. Gulati GS, Kothari SS. Diffuse infiltrative cardiac tuberculosis. Ann Pediatr Cardiol 2011;4:87–9. 4. Thachil A, Christopher J, Sastry BK, et al. Monomorphic ventricular tachycardia and mediastinal adenopathy due to granulomatous infiltration in patients with preserved ventricular function. J Am Coll Cardiol 2011;58: 48–55.
fraction (mean 46.7 14.4% to 50.8 16.1%; p ¼ 0.009). All patients but 1 became free of VT. In a follow-up PET/CT (n ¼ 11), abnormal metabolic activity resolved completely in the myocardium in 4 patients and in the lymph nodes in 9 patients (Table 1). There were no deaths.
Increased Mortality by Digoxin in Patients With Atrial Fibrillation?
Our observations suggest that TB can present as idiopathic VT or unexplained ventricular dysfunction;
In the TREAT-AF (Retrospective Evaluation and
patients may not have constitutional symptoms.
Assessment of Therapies in AF) study (1), the effect of
Biopsy
targeting
fluorodeoxyglucose-avid
lymph
digoxin on overall mortality in patients with incident
nodes rather than endomyocardial biopsy is more
atrial fibrillation (AF) was studied. In this observa-
useful in making a clinical diagnosis. It may be prudent
tional study, after adjustment for potential con-
to investigate all patients with unexplained VT or left
founders with the Cox proportional hazards model
ventricular dysfunction and lymphadenopathy for
and propensity score analyses, digoxin was associ-
myocardial TB, especially in those areas where the
ated with an increased risk (21% to 24%) of death. The
prevalence of TB is high. By subjecting the biopsy
investigators extensively discussed the potential
specimen to mycobacterial culture, TB polymerase
limitations of their study, but I have 2 questions
chain reaction and histopathologic examination will
about the design choices.
help in distinguishing between TB and sarcoidosis—
First, the investigators stated that patients were
another granulomatous condition that may present in
placed in the digoxin group versus the reference
a similar fashion (4). This report serves to highlight the
group on the basis of use of digoxin within the first
fact that myocardial TB may be more common than
90 days after the diagnosis of AF. Digoxin is the first
believed. Early diagnosis is important to prevent
choice for therapy in patients with AF complicated by
morbidity and mortality.
heart failure and the second choice in patients whose
Alladi Mohan, MD Ajit Thachil, MD, DM Gomathi Sundar, PG, PA B.K.S. Sastry, MD, DM Ashfaq Hasan, MD C. Sridevi, MD, DNB *Calambur Narasimhan, MD, DM *CARE Hospital Department of Cardiac Electrophysiology Road No. 1, Banjara Hills Hyderabad, Telangana India 500 034 E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2014.09.087 Please note: Dr. Narasimhan has received research grants from Biosense Webster, Inc., Medtronic, Inc., and St. Jude Medical, Inc.; and a fellowship grant from Medtronic, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors thank John G. Cleland, Foundation Chair of Cardiology at the University of Hull, for useful suggestions.
first choices for treatment of AF, beta-blockers and calcium
channel
antagonists,
are
not
effective
enough. When only the first 90 days are used for exposure classification, there may be a substantial misclassification of digoxin in both the digoxin group and the reference group. The fact that the medication possession ratio of digoxin was only calculated for the digoxin group does not take into account such misclassification. Second,
the
investigators
stated
that
they
adjusted for the medication possession ratio in the multivariate Cox analysis. I do not understand this: how can you adjust for a variable that is zero in all patients in the reference group and a certain number between zero and one in the digoxin group? I believe the appropriate analysis would be to stratify the digoxin group with different medication possession ratios and compare these with the reference group.